Ventricular assist device

ABSTRACT

A control device ( 100 ) for controlling the rotational speed (n VAD (t)) of a non-pulsatile ventricular assist device, VAD, ( 50 ) uses an event-based within-a-beat control strategy, wherein the control device is configured to alter the rotational speed of the VAD within the cardiac cycle of the assisted heart and to synchronize the alteration of the rotational speed with the heartbeat by at least one sequence of trigger signals (σ(t)) that is related to at least one predetermined characteristic event in the cardiac cycle. Further, a VAD ( 50 ) for assistance of a heart comprises the control device ( 100 ) for controlling the VAD, wherein the VAD is preferably a non-pulsatile rotational, for example catheter-based, blood pump.

FIELD OF THE INVENTION

The present invention concerns the field of non-pulsatile ventricularassist devices (VAD). In particular, the invention relates to a controldevice for within-a-beat control of a non-pulsatile VAD, such as anintravascular rotary blood pump, and a VAD comprising the control devicefor controlling the VAD.

BACKGROUND

If the pumping function of a patient's heart is insufficient despiteoptimal medical treatment, the circulatory system can be assisted by aVAD. VADs may assist or even substitute the insufficient ventricularpumping function of a heart by delivering blood parallel to theventricle of the heart. To this end, a VAD typically is configured totake blood from the blood circulation at an inlet to eject it back tothe blood circulation at an outlet. In doing so, the VAD needs toovercome the pressure difference between the outlet and the inlet, i.e.between after-load and pre-load of the VAD.

One particular example of a VAD is a catheter-based rotary blood pumpthat is arranged to be placed or implanted directly into the heart forseveral hours or days for assisting the heart function until recovery.U.S. Pat. No. 5,911,685 A discloses an exemplary intravascular rotaryblood pump. However, there are other types of VADs as well.

In patients receiving heart assistance by a non-pulsatile blood pump, anincreased tendency to bleeding has been observed. The increased tendencyto bleeding has been associated with a deficit in a particular bloodglycoprotein known as von Willebrand factor (vWF) that is involved inhemostasis.

The term “cardiac cycle” used herein embraces the dynamic behavior ofthe heart during one heartbeat including e.g. the time-dependent changesof blood pressure and ventricular volume. The heartbeat herein isdefined to start with the evocation of the atrial contraction, and toend right before the following atrial contraction, distinguishingbetween systole and diastole. The systole of the heart (also called theejection phase of the heart) is the phase between the closing of themitral valve and the closing of the aortic valve. The diastole (alsocalled the filling phase of the heart) is the phase between the closingof the aortic valve and the closing of the mitral valve. The frequencyof the heart passing through the cardiac cycle is known as the heartrate.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an improvedassistance to the circulatory system of a patient by which theabove-observed vWF deficiency can be avoided or at least reduced.

In particular, it is an object of the present invention to provide asmart control device for a VAD, such as a rotary blood pump, whichoperates the VAD with the aim of avoiding or at least reducing the sideeffect of applying a non-pulsatile VAD resulting in vWF deficiency.

In particular, it is a further object of the present invention toprovide a smart control device for a VAD which operates the VAD so that,besides avoiding or at least reducing the side effect of the applicationof a non-pulsatile VAD, a required blood pressure is provided, which isrelated to the patient's current perfusion demands.

It has been found by the inventors that when a minimum residualpulsatility of the blood pressure is restored and/or maintained in thecirculatory system, the above-discussed increased tendency to bleedingis reduced. Additionally, a sufficient pressure pulsatility also seemssupportive of a sufficient perfusion of the microvasculature of thecirculatory system.

Thus, the main idea of the present invention is an event-basedwithin-a-beat control strategy which extends a control loop for therotational speed of the VAD by a speed command signal generator forgenerating a speed command signal for the alteration of the rotationalspeed of the VAD, so that a predetermined desired minimum pulsatility isachieved either in a first setup by an open-loop control, wherein thespeed command signal is alternated between predefined rotational speedlevels or in a second setup by a closed-loop pressure control in afeedback system, wherein the speed command signal is automatically setfor each heartbeat by an additional outer pressure control loopresulting in a cascade control.

The proposed event-based within-a-beat control strategy for the bloodpressure, in one particular embodiment, enables the pulsatility of thepatient's blood pressure to be affected by changing the blood flowthrough the VAD within a cardiac cycle of the heart. One particularapplication of this event-based within-a-beat control strategy for theblood pressure can be to restore and/or maintain the desired minimumpulsatility of the arterial blood pressure, thus avoiding the assumedside effect of the VAD application on the vWF release. This is supportedby the fact that it has been observed that most continuous flow VADsreduce the pulsatility and thus lead to reduced vWF appearance.

Thus, the event-based within-a-beat control strategy proposed herein forthe rotational speed of the VAD is particularly useful for avoiding theinherent side effect of non-pulsatile VADs with respect to vWFdeficiency. In other words, the particular proposed speed alteration forrestoration and/or maintenance of a desired minimum pulsatility of theblood pressure is not considered as a therapy but rather as a featurefor eliminating the inherent side effect of non-pulsatile VADs.

Moreover, the alteration of the pump speed within a cardiac cycle(hereinafter also referred to as “heartbeat” or “beat”) generatesfurther advantageous effects compared to non-pulsatile heart assistance,such as improved perfusion of the microvasculature of the circulatorysystem.

In the context of restoring and/or maintaining the desired minimumpulsatility of the arterial blood pressure, the term “pulsatility” usedherein is generally understood as the difference

ΔAoP(h)=AoP|_(max)(h)−AoP|_(min)(h)

between the maximum aortic pressure AoP|_(max)(h) and the minimum aorticpressure AoP|_(min)(h) during the h^(th) cardiac cycle.

In the following, for the sake of simplification, all characteristicmeasurement values and calculated values will just be referenced to aconcrete (j−1)^(st), j^(th), (j+1)^(st), and so on, heartbeat or a moregeneral h^(th) heartbeat, which also implies the dependence of thevalues on continuous time t and on concrete measurement points k. Forexample,

AoP|_(max)(j)=max_(k){AoP(t _(j,k))} for k=0 . . . m _(j)

with the index j indicating the j^(th) heartbeat, and the maximum of thesignal AoP is calculated for the j^(th) heartbeat over all k=0 . . .m_(j) measurement values of the signal AoP starting with the firstmeasurement point of the j^(th) heartbeat k=0, and ending with the lastmeasurement point k=m_(j) right before the next (j+1)^(st) heartbeatstarts. Then

AoP|_(max)(j+1)=max_(k){AoP(t _(j+1,k))} for k=0 . . . m _(j+1)

and so on.

The inventors assume that restoration and/or maintenance of a minimumresidual pulsatility is desirable, particularly in the case of aVAD-assisted circulatory system. Accordingly, the main idea of thisinvention is to improve the control of a non-pulsatile VAD so thatduring the cardiac cycle, i.e. within one heartbeat, the rotationalspeed n_(VAD)(t) of the VAD is altered so that a desired minimumpulsatility Δ

(h) is generated which is intended to restore and/or maintain a minimumresidual pulsatility in the artery of interest, i.e. in the aorta in thecase of left-sided heart assistance. The definitions of different typesof pulsatility are as follows (see also FIG. 3a )):

ΔAoP(h)=AoP|_(max)(h)−AoP|_(min)(h)  Physiologic (non-assisted)pulsatility:

Δ

(h)=

|_(max)(h)−

_(min)(h)  Desired (assisted) minimum pulsatility:

ΔAoP_(purse)(h)=Δ

(h)−ΔAoP(h)  Pulsatility difference:

Accordingly, the desired minimum pulsatility Δ

(h) depends on the maximum and minimum desired aortic pressure

|_(max)(h) and

|_(min)(h), respectively, within the h^(th) cardiac cycle. Thepulsatility difference ΔAoP_(pulse)(h) is defined to be the differencebetween the current physiologic (non-assisted) pulsatility ΔAoP(h) andthe desired (assisted) minimum pulsatility Δ

(h).

In this regard, the inventors have further found that predeterminedvalues for the desired minimum pulsatility are in the range of Δ

(h)=[15 . . . 30] mmHg, but the desired minimum pulsatility Δ

(h) may be higher, as well.

One further point found by the inventors is that a physical prerequisitethat preferably has to be fulfilled by the VAD to be used for the hereindisclosed applications is the absence of relevant inertia. That is tosay, the VAD is preferably a low inertia device. Up to now, rotary bloodpumps, for example, such as the above-mentioned catheter-based pump,which have a negligibly small mass moment of inertia are perfectlysuited for speed control scenarios with within-a-beat speed alterations,whilst being highly energy efficient, e.g. avoiding thermal dissipationlosses. Particular characteristics for achieving the VAD having a smallmass moment of inertia are, inter alia, i.e. not exclusively: moving, inparticular rotating, parts of the VAD comprise low masses, for example arotor or impeller may be made of a low weight material, such as plasticmaterials, synthetic materials or the like; a driving means, such as anelectric motor, is arranged near, preferably very near, most preferablyadjacent, to the rotor or impeller, so that a shaft coupling the motorwith the rotor or impeller can be kept short, thereby keeping therotating mass thereof low (for instance, devices are known that have arotating drive cable or wire for coupling a rotor to the motor, whichwould be undesirable as the mass of the cable or wire increases the massto be accelerated or decelerated); all moving, in particular rotating,parts have small diameters, so that the resulting mass moment of inertiaof the parts can be kept small.

A first aspect of the invention provides a control device which altersthe rotational speed (in the following just “speed”) n_(VAD)(t) of anon-pulsatile VAD within a cardiac cycle with respect to physiologicalconditions in an event-based manner.

To this end, the control device can be configured to alter the speed ofthe VAD within a cardiac cycle of the assisted heart and, in combinationwith a trigger signal generator, to synchronize the alteration of aspeed command signal n_(VAD)(t) for speed with the heartbeat by using atleast one event sequence that is related to at least one predeterminedcharacteristic recurring event within the cardiac cycle. Thus, thenative cardiac output of the assisted heart can be affected by theVAD-induced blood flow Q_(VAD)(t).

In a particular embodiment, the control device may be configured toadjust the speed command signal n_(VAD) ^(set)(t) for either apredetermined pulse duration τ^(pulse)(h) or a heart rate dependentpulse duration τ^(assist)(g) compared to a basic speed level n_(VAD)^(set,basic)(h) to generate a desired minimum pulsatility ΔAoP(h)=Δ

(h) in an artery of interest by the resulting blood flow through the VADwithin the h^(th) cardiac cycle.

An artery of interest may be at least the aorta, if the VAD isconfigured for left-sided heart assistance. Alternatively, an artery ofinterest may be at least the pulmonary artery, if the VAD is configuredfor right-sided heart assistance.

To this end, the control device may be configured to adjust the speedcommand signal n_(VAD) ^(set)(t) of the VAD and to control the speedn_(VAD)(t) of the VAD satisfying the desired minimum pulsatility Δ

(h) either a first setup or a second setup.

In the first setup, the control device can be arranged to adjust thespeed command signal n_(VAD) ^(set)(t) in an open-loop manner, e.g. by acommand signal generator. In the first setup, the desired minimumpulsatility Δ

(h) can be caused by alternating the speed command signal n_(VAD)^(set)(t) of the VAD between predefined speed levels using anevent-based command signal generator.

In the second setup, the control device can be arranged to adjust thespeed command signal n_(VAD) ^(set)(t) in a closed-loop feedback manner,e.g. by extending a speed control loop for the speed n_(VAD)(t) of theVAD by an additional pressure control loop resulting in a cascadecontrol strategy. In the second setup, the speed command signal n_(VAD)^(set)(t) may be automatically set in the speed command signalgenerator, e.g. by an outer loop with a feedback pressure controlstrategy, so that the desired minimum pulsatility Δ

(h) can be achieved for the h^(th) heartbeat while takingphysiologically induced boundary conditions into consideration. Thefirst setup may also take physiologically induced boundary conditionsinto consideration.

Such boundary conditions may be e.g. limited available blood volumeand/or maximum and/or minimum levels of mean arterial blood pressureAoP(h). For the control device to work within the physiologicalconstraints it may be desirable to monitor the ventricular fillingpressures (e.g. with a pressure sensor in the ventricle) or any event ofsuction, which may occur due to the lack of blood volume (e.g. with apressure sensor, which is located within or at the VAD inlet to monitorsuction-related negative inflow pressures).

The open-loop setup (first setup) and the closed-loop setup (secondsetup) for the generation of the speed command signal n_(VAD) ^(set)(t)may both be configured to operate in an event-based manner, and may bothbe intended to generate the desired minimum pulsatility Δ

(h) during the h^(th) heartbeat by adjusting the speed command signaln_(VAD) ^(set)(t) of the VAD for the predetermined pulse durationτ^(pulse)(h).

The control device may consist of an inner control loop for controllingthe speed n_(VAD)(t) of the VAD and an outer loop, the structure ofwhich depends on the first or second setup defined above. For the inner(speed) control loop, a common high speed feedback closed-loop controlcan be used. In the following, the focus will be on the generation ofthe speed command signal n_(VAD) ^(set)(t) of the VAD for the innercontrol loop.

Preferably, the control device is configured to synchronize theadjustment of the speed command signal n_(VAD) ^(set)(t), such as thebeginning and/or the end of a command signal pulse, with the heartbeatby using at least one sequence of trigger signals σ(t) that is relatedto at least one predetermined characteristic event in the cardiac cycle.

For example, the control device may be configured to adjust the speedcommand signal n_(VAD) ^(set)(t) so that the blood pressure in theartery of interest produced by the VAD is increased for a predefinedtime interval of the cardiac cycle. In general, the control device maybe configured to set the speed command signal n_(VAD) ^(set)(t) foradjusting the VAD speed at a high level during systole and/or at a lowlevel during diastole.

For example, the desired minimum pulsatility may be generated by speedalteration during the systole of the assisted heart only. That is tosay, the speed command signal n_(VAD) ^(set)(t), which defines thetarget speed level, may be adjusted by increasing a basic speed leveln_(VAD) ^(set)(t)=n_(VAD) ^(set,basic)(h) to a target speed leveln_(VAD) ^(set)(t)=n_(VAD) ^(set,basic)(h)+Δn_(VAD) ^(set)(h) before, ator slightly after the beginning of the systole of the assisted heart,and may be reduced again to the basic speed level n_(VAD)^(set,basic)(h) before, at or slightly after the end of the systole. Inthis way, the increase of the basic speed level n_(VAD) ^(set,basic)(h)by adding a speed difference Δn_(VAD) ^(set)(h) generates a positivespeed pulse during the systole of the assisted heart.

Correspondingly, the desired minimum pulsatility may be generated byspeed alteration during the diastole of the assisted heart only. That isto say, the speed command signal n_(VAD) ^(set)(t) may be adjusted bydecreasing the speed level from the basic speed level n_(VAD)^(set,basic)(h) to the target speed level n_(VAD) ^(set)(t)=n_(VAD)^(set,basic)(h)−Δn_(VAD) ^(set)(h) before, at or slightly after thebeginning of the diastole of the assisted heart, and may be increasingthe speed level to the basic speed level n_(VAD) ^(set,basic)(h) againbefore, at or slightly after the end of the diastole. In this way, thedecrease of the basic speed level n_(VAD) ^(set,basic)(h) by subtractinga speed difference Δn_(VAD) ^(set)(h) generates a negative speed pulseduring the diastole of the assisted heart.

However, speed command signal alteration during the systolic phase orthe diastolic phase is respectively one generic example ofsynchronization of the speed variation with the heartbeat. It will beappreciated that the desired minimum pulsatility Δ

(h) may be generated by a combination of both a positive speed pulseduring systole and a negative speed pulse during diastole.

Note that the reason for the speed command signal alteration to besynchronized with the cardiac cycle is to enhance the residualpulsatility of the weakened heart, which is due to the native heartcontraction in systole. Preferably, the speed command signal alterationresults in systolic flow contribution to the native ejection of theheart alone; i.e. a co-ejection of the heart and the VAD is desirable.

Thus, in the first embodiment, restoration and/or maintenance of thedesired minimum pulsatility can be achieved by the control device beingconfigured to alter the speed command signal n_(VAD) ^(set)(t) foradjusting the speed of the VAD so that the VAD-induced blood flowQ_(VAD)(t) is reduced substantially during the diastole of the cardiaccycle and/or is increased substantially during the systole of thecardiac cycle. Thus, the desired minimum pulsatility of the arterialblood pressure can be restored and maintained. The diastolic speedreduction of the VAD may allow the ventricle to fill adequately, so thata systolic co-ejection of blood volume from the VAD and the native heartis possible.

The inventors have found that, as an aim for the speed command signalalteration, the native heart and the VAD both preferably provideadequate systolic peak flow rates so that the total peak flow perheartbeat

Q _(total|max)(h)=Q _(heart|max)(h)+Q _(VAD|max)(h)

and the total ejected volume (EV) per heartbeat

EV(h)=EV_(heart)(h)+EV_(VAD)(h)

result in an adequate increase in systolic systemic blood pressure. Thenative heart's ability to co-eject may depend on the ventricularpreload, on the ventricular filling level, and on the level of heartcontractility as well as on the achievable peak flow of the VAD. Thenative heart's ability to co-eject may also depend on the patient's bodymass index, or body surface, or the vascular compliance as well as theperipheral resistance.

For example, a generic patient with a height of 1.75 m and a weight of75 kg has approximately a mean blood flow of 5 L/min. The demand can beestimated based on a person's body surface area (BSA). The genericpatient has a body surface area of about 1.9 m² (based on the formula byR. D. Mosteller, “Simplified calculation of body-surface area”, N. Engl.J. Med. 317, No. 17, October 1987, p. 1098). The normal blood flownormalized to the BSA equals approximately 2.6 L/m². A mean blood flowof 5 L/min in a healthy patient at rest results in a blood pressure ofabout 120 mmHg to 80 mmHg.

A total peak flow Q_(total|max)(h) of about 8 L/min during systole isconsidered sufficient to result in a desired minimum pulsatility Δ

(h) of about 15 mmHg in a normal-sized person (BSA 1.9 m²). Thus, moregenerally, a total peak flow of 8 L/min divided by 1.9 m² and multipliedby the patient's actual BSA may result in a more patient-adapted valueof peak flow. As another example, a patient with BSA=1.6 m² may have anequal desired minimum pulsatility Δ

(h) with just Q_(total|max)(h)=6.7 L/min total peak flow during systole.Taking into account all the variability in compliance and peripheralresistance more generally, a total peak flow between 6 L/min and 10L/min should be sufficient for the vast majority of patients treatedwith an assist device to gain a target desired minimum pulsatility of atleast Δ

(h)≥15 mmHg. Accordingly, systolic peak flow rates resulting in a totalpeak flow of

Q _(total|max)(h)=Q _(heart|max)(h)+Q _(VAD|max)(h)>6 L/min . . . 10L/min

which result in total ejected volumes of

EV(h)=EV_(heart)(h)+EV_(VAD)(h)=40 ml . . . 70 ml

are desired so that the desired minimum pulsatility Δ

(h)>[15 . . . 30] mmHg can be achieved.

The desired minimum pulsatility Δ

(h) will not be a fixed value, but may vary based on the recruitment ofvWF. Simulation results have underlined the fact that the command signalgenerator or the outer pressure control loop can either focus onincreased pulsatility while accepting reduced mean aortic pressure orfocus on increased mean aortic pressure while accepting reducedpulsatility.

The duration of systole at normal heart rate HR≈70 bpm (beats perminute) in humans is normally about τ^(Systole)(h)=300 ms and variesonly marginally with heart rate. Patients in a state of shock arecommonly characterized, inter alia, by a heart rate of up to HR≤120 bpm.Thus, a minimum duration of a cardiac cycle is assumed at τ(h)=500 ms.Further, in patients with a higher heart rate HR≥120 bpm, a shortenedduration of systole is assumed at about τ^(Systole)(h)=250 ms.

Therefore, the predetermined pulse duration τ^(pulse)(h) of the speedpulse may be in the range of τ^(pulse)(h)=[200 . . . 300] ms, preferablyτ^(pulse)=[225 . . . 275] ms, most preferably about τ^(pulse)(h)=250 ms.

Alternatively, the predetermined pulse duration τ^(pulse)(h) of thespeed pulse may be in the range of +/−50% or +/−100 ms of the durationof the systole Σ^(Systole)(h) of the assisted heart.

Depending on the residual pulsatility in the artery of interest, thepulse duration of the speed pulse may also be adapted to the heart rate,resulting in a time interval τ^(assist)(h), which preferably dependse.g. on the observations of preceding heart rates and the durations ofpreceding systolic phases.

Additionally or alternatively, the adjustment of the speed commandsignal n_(VAD) ^(set)(t) may be synchronized with the appearance of theR wave in an electrocardiogram (ECG) signal of the patient and/or set toa constant repetition rate e.g. in the case of cardiac arrest.

In a possible practical implementation, the VAD, e.g. in the form of arotational blood pump, may comprise an actuator, for instance arotational motor, for driving the blood pump, which produces theVAD-induced blood flow Q_(VAD)(t). Then, the control device may alterthe speed n_(VAD)(t) of the VAD by adjusting the speed command signaln_(VAD) ^(set)(t) to the target speed level for the rotational motor andcontrolling the speed n_(VAD)(t) of the VAD by a feedback closed-loopcontrol. Accordingly, the modification of the pulsatility, i.e. thepulsatility difference ΔAoP_(pulse)(h), may be associated with acorresponding adjustment of the speed command signal n_(VAD) ^(set)(t),e.g. by a speed difference Δn_(VAD) ^(set)(h), i.e. the speed commandsignal n_(VAD) ^(set)(t) of the rotational motor is increased from abasic speed level n_(VAD) ^(set,basic)(h) by the speed differenceΔn_(VAD) ^(set)(h) for generating the desired minimum pulsatility Δ

(h) which is set by the control device. Thus, the control device may beconfigured to vary the corresponding higher speed command signal n_(VAD)^(set)(t)=n_(VAD) ^(set,basic)(h)+Δn_(VAD) ^(set)(h) to achieve thedesired minimum pulsatility Δ

(h).

In general, the speed difference Δn_(VAD) ^(set)(h) may also benegative, e.g. to generate a negative speed pulse.

It is noteworthy that a desired speed difference Δn_(VAD) ^(set)(h) maybe determined based on the achieved pulsatility differenceΔAoP_(pulse)(h), which is largely a function of how much blood volume isdelivered to the arterial system in a given time unit. It needs to beunderstood that any arterial blood pressure built-up is the end resultof blood volume being ejected during a time unit into the arterialsystem with its intrinsic compliance and peripheral resistance.

Preferably, the control device is further configured to adjust the speedcommand signal n_(VAD) ^(set)(t) also outside the speed alterationinterval, e.g. to adjust the basic speed level n_(VAD) ^(set,basic)(h),so that a predetermined mean arterial blood pressure AoP(h) is achievedby the VAD or to avoid any backflow into the ventricle via the pump,which is called regurgitant pump flow.

In a further development, the control device, in particular in thesecond closed-loop setup, may be configured to adjust the speed commandsignal n_(VAD) ^(set)(t) both within and outside the speed alterationinterval to achieve the desired minimum pulsatility Δ

(h).

In a further development, the control device may additionally beconfigured to adjust the speed command signal n_(VAD) ^(set)(t) whiletaking into consideration the mean arterial blood pressure per heartbeatAoP(h) as a control constraint.

For example, the control device may be configured to adjust the speedcommand signal n_(VAD) ^(set)(t) to avoid a drop of the mean arterialblood pressure AoP(h) below a predetermined threshold value AoP_(thr)(h).

Additionally, the control device may be configured to adjust the speedcommand signal n_(VAD) ^(set)(t) so that the speed alteration interval(or speed pulse) is started at a predetermined time interval τ^(incr)(h)before a predetermined characteristic event occurs. This means that thespeed change may be induced a time interval τ^(incr)(h) before, e.g., anexpected or predicted beginning of the ventricular contraction of theassisted heart, which may be the corresponding characteristic event inthe cardiac cycle. This may be of particular importance, since thedynamic response of a particular VAD, e.g. a specific pump, may bedelayed due to a pump-specific mechanical and/or hydraulic inertiarequiring a latency before the desired effect is provided.

For example, the beginning of the heart contraction, which is definede.g. by the time of mitral valve closure, may be detected based on acorresponding blood pressure signal. For example, if the VAD isconfigured for left-sided heart assistance the corresponding bloodpressure signal may be the left ventricular pressure.

For example, the atrial contraction preceding the ventricularcontraction may be detected. Thus, the event occurs earlier then theevent of systolic contraction, allowing the pump to speed up when thebeginning of atrial contraction is used as the event.

Alternatively or additionally, the predetermined event may be theoccurrence of the R-wave in an ECG signal of the assisted heart.

The time interval τ^(incr)(h) may be useful for taking account of thefact that the speed increase of the VAD is slowed down by hydraulicimpacts of the blood on the drive of the VAD. Hence, to increase thespeed, the speed command signal n_(VAD) ^(set)(t) should be increased bya smooth trajectory to avoid hemolysis or other undesired hemodynamicside effects, such as suction or VAD-induced cavitation, when bloodwould be accelerated too fast.

Additionally, the control device may be configured to end the pulse ofthe speed command signal n_(VAD) ^(set)(t) after the predetermined pulseduration τ^(pulse)(h).

Alternatively, the control device may be configured to end the pulse ofthe speed command signal n_(VAD) ^(set)(t) after a heart rate dependentpulse duration τ^(assist)(h), i.e a pulse duration that is adapted bythe control device to the heart rate HR(h). In particular, the controldevice may be configured to end the pulse of the speed command signaln_(VAD) ^(set)(t) when at least one predetermined characteristic eventof the cardiac cycle occurs.

Additionally, the control device may be configured to end the pulse ofthe speed command signal n_(VAD) ^(set)(t) a predetermined time intervalτ^(red)(h) before or when at least one predetermined characteristicevent of the cardiac cycle occurs.

For example, the predetermined characteristic event may be the beginningof the relaxation of the assisted heart and/or the closing of the aorticvalve.

For example, at least one event may be the beginning of relaxation ofthe assisted heart. Accordingly, the control device may be configured toderive the occurrence of an event based on a signal that comprisesinformation about characteristic events such as the beginning ofrelaxation. As a result, the pulse of the speed command signal n_(VAD)^(set)(t) can be synchronized e.g. with the time of occurrence of themaximum drop in pressure within the ventricle of the assisted heart.Note that the time of maximum drop in pressure marks the beginning ofventricular relaxation (relaxation moment) after the preceding systole.

Alternatively or additionally, the control device may be configured toderive the occurrence of at least one event per cardiac cycle based onat least one internal signal of the control device. “Internal signal” ofthe control device means herein that the signal is a signal which isalready internally available to the control device for analysis, such asa control signal provided by the control device to the VAD.

For example, the at least one internal signal may be an electricalcurrent provided to actuate the VAD, such as a motor current supplied tothe VAD. Thus, the control device may be configured to derive theoccurrence of at least one event per cardiac cycle based on the analysisof the electrical current signal and/or a processed version thereof, forexample a time derivative, e.g. the first time derivative.

For example, the VAD may be the above-mentioned rotational blood pump.The blood pump may comprise an actuator, such as a rotational electricalmotor, for driving a rotational thrust element, such as an impeller, forproducing a corresponding blood flow. In operation of the blood pump, amotor current is consumed by the motor in order to achieve a respectivetarget speed level, according to the set speed command signal n_(VAD)^(set)(t), of the motor and the rotational thrust element. The requiredmotor current I_(VAD)(t) for achieving the target speed depends on thecurrent blood pressure difference Δp(t) the blood pump needs toovercome, such as the difference between the blood pressures within theaorta AoP(t) and within the left ventricle LVP(t),

Δp(t)=AoP(t)−LVP(t).

In other words, the electrical current supplied to the blood pumpcorresponds directly to the electrical current required by the motor ofthe blood pump to achieve the set speed

I _(VAD)(t)=f(n _(VAD) ^(set)(t),Δp(t)).

Thus, the motor current supplied to the VAD by the control device or bya supply unit controlled by the control device can be used as aninternal signal to derive the occurrence of at least one event percardiac cycle.

Furthermore, the control device may be further configured to estimatethe current VAD-induced blood flow Q_(VAD)(t), which is based on theelectrical current signal and on known calculation specifications with apump characteristic correlation between motor current at a given speed,pump flow and pressure difference.

Alternatively or additionally, the control device may be configured toderive the occurrence of at least one event per cardiac cycle from atleast one external signal provided to the control device. “Externalsignal” means herein that the signal is a signal which is received bythe control device from external sensors such as one or more bloodpressure sensors of the VAD and/or from external devices such as apatient monitoring unit or an electrocardiograph (ECG). Such externalsignals can be fed into the control device via corresponding interfacesor input terminals, to be available in the control device for processingand/or analysis by the control device.

For example, the measuring signal may represent at least one of a bloodpressure difference Δp(t) between an outlet of the VAD and an inlet ofthe VAD, a blood pressure in a ventricle of the assisted heart LVP(t), ablood pressure in the aorta AoP(t) adjacent to the assisted heart, ablood pressure in the vena cava CVP(t) adjacent to the assisted heart, ablood pressure in the pulmonary artery PAP(t) adjacent to the assistedheart, just to give some examples. The waveforms of all of thesemeasuring signals may contain information descriptive of the time ofoccurrence of particular characteristic events in the cardiac cycle.

For example, if the VAD is the above-discussed rotational blood pump, itmay comprise an inlet for sucking in blood from the heart, e.g. from theinside of a ventricle, and an outlet for ejecting blood to a vesseladjacent to the heart, such as the artery of interest, which may be theaorta or pulmonary artery depending on whether the VAD is inserted tothe left side or the right side of the heart.

For example, as published e.g. in U.S. Pat. No. 5,911,685 A, the VAD maycomprise at least one of a pressure sensor for measuring the bloodpressure at the inlet of the VAD, such as a ventricular pressure in theassisted heart, and a pressure sensor for measuring the blood pressurein a vessel adjacent to the heart, such as the blood pressure in theaorta or pulmonary artery adjacent to the assisted heart. Alternativelyor additionally, the VAD may comprise one differential pressure sensorfor measuring the differential blood pressure between the outlet and theinlet of the VAD.

Additionally, the control device may be configured to receive, store andanalyze at least one measuring signal which contains information aboutcharacteristic points of the cardiac cycle, and which can be used toestimate the current working phase of the heart in the cardiac cycle.Then, the control device may be configured to predict the time ofre-occurrence of a particular characteristic during the next cardiaccycle based on information about previous cardiac cycles.

Basically, in all embodiments, the at least one measuring signal may beat least one of an ECG signal, a measuring signal representing the bloodpressure in the left ventricle or the right ventricle of the heart, ameasuring signal of the blood pressure in the vena cava or the aorta orin the pulmonary artery adjacent to the heart.

Thus, for predicting the next time of occurrence of at least one eventbased on information on previous cardiac cycles, the chosen signal maypreferably contain information about the cardiac cycle, so that the timeof occurrence of at least one event per cardiac cycle can be predictedbased on the chosen measurement signal and on detected events duringprevious cardiac cycles.

Additionally or alternatively, the control device may be configured toeliminate the effect of active heart assistance by the VAD on themeasuring signals from said measuring signals. In particular, thecontrol device may be configured to analyze at least two, preferablyindependent, measuring signals by data fusion with the aim of detectingthe predetermined events in a cardiac cycle despite the effect of theVAD-induced pressure change on the cardiac dynamic behavior.

In particular embodiments, the control device may be configured to setthe speed of the VAD so that in the diastolic phase of the cardiac cycleof the assisted heart the amount of blood ejected by the VAD into theartery of interest, such as the aorta or the pulmonary artery, is lowenough such that a blood volume remains in the corresponding ventricleand the co-ejection of the VAD and the ventricle during systole resultsin a preferred minimum peak blood flow, i.e. the minimum peak blood flowis preferably about 6 L/min, more preferably 7 L/min, most preferably 8L/min and more (as discussed above).

The systolic peak flow will largely depend on the native heart's abilityto co-eject, depending specifically on the ventricular preload, theventricular filling level, and the level of heart contractility as wellas the achievable peak flow of the VAD. The total peak flow perheartbeat Q_(total|max)(h) and the total ejected volume per heartbeatEV(h) will need to result in an adequate increase in systolic systemicblood pressure, as described above. This, however, also depends on thepatient's body mass index, or body surface, the vascular compliance aswell as peripheral resistance. In other words, a minimum total peak flowof Q_(total|max)(h)=6 L/min may be sufficient in a small patient, but ahigher total peak flow may be required in a larger patient (as discussedabove). A higher total peak flow may especially be required if thevascular bed is relaxed or wide open.

Additionally, the control device may be configured to adjust the speedcommand signal n_(VAD) ^(set)(t) in the form of a pulse during thecardiac cycle only if the resulting mean arterial blood pressure perheartbeat AoP(h) does not drop below a predetermined threshold value AoP_(thr)(h).

The minimum VAD-induced blood flow Q_(VAD)(h) may correspond to arequired minimum heart assistance to be provided by the VAD to aweakened heart. The idea is that the VAD can be operated so as both toobtain the desired recruitment of vWF and to ensure that a requiredminimum blood flow is provided. For example, currently required bloodflow may be related to a patient's current perfusion demand, taking intoconsideration periods of required high assistance, e.g. daytimeactivity, walking, climbing stairs, and so on, in which case the VADwill run at relatively high mean speeds. Periods of low patientperfusion demands, e.g. at rest, while sleeping, etc., can be used torun the VAD at lower mean speeds. This will help to increase pulsatilityand assist the recruitment of vWF while still maintaining some degree ofblood flow support. Of course a more sophisticated regime is possible inwhich the current demand for heart assistance corresponding to aparticular, e.g. average, VAD-induced blood flow Q_(VAD)(h) is takeninto consideration in a continuous manner. Thus, the control device maybe configured to use any available surplus between a currently requiredminimum blood flow and the maximum blood flow that the VAD may providefor the restoration and maintenance of a residual pulsatility asproposed here.

It is noted that it can further be advisable to synchronize thealteration of the speed in a “y in x” manner, i.e. the proposed speedpulse is generated only in y out of x consecutive cardiac cycles. Forexample, a speed pulse aiming to restore or maintain a desired minimumpulsatility may be induced in a one in two or one in three or one infour manner or in a two in three or two in four or two in five manner,i.e. in one cardiac cycle in every two or in every three or in everyfour consecutive cardiac cycles and in two cardiac cycles in every threeor in every four or in every five consecutive cardiac cycles,respectively. This may be particular beneficial if the heart frequencyis too high or if the level of pump assistance for the heart is notadequate. Thus, an augmented pulsatility is only providedintermittently. It has been found that this can serve the purpose of vWFrecruitment perfectly. For example, the control device can additionallybe configured to set the speed n_(VAD)(t) of the VAD, during at least yof the other (x-y) consecutive cardiac cycles of the assisted heart sothat the mean arterial blood pressure per heartbeat remains above thepredetermined threshold value (AoP(h)≥AoP _(thr)(h)).

Finally, the above-discussed functions or functionalities of the controldevice can be implemented by a corresponding computing unit, in hardwareor software or any combination thereof, of the control device. Suchcomputing unit can be configured by means of corresponding computerprograms with software code for causing the computing unit to performthe respectively required control steps. Such a programmable computingunit is well known in the art and to the person skilled in the art andtherefore need not be described here in detail. Moreover, the computingunit may comprise particular dedicated hardware useful for particularfunctions, such as one or more signal processors for processing and/oranalyzing e.g. the discussed measuring signals. Further, respectiveunits for controlling the speed of a drive of the VAD may be implementedby respective software modules as well.

The corresponding computer programs can be stored on a data carriercontaining the computer program. Alternatively, the computer program maybe transferred, e.g. via the Internet, in the form of a data streamcomprising the computer program without the need of a data carrier.

A second aspect of the invention provides a VAD comprising one of thecontrol devices according to the first aspect of the invention. Forexample, the VAD may be a rotational blood pump, i.e. a blood pumpdriven by a rotational motor.

For example, such blood pump may be catheter-based to be implanted orplaced directly into a heart via corresponding blood vessels.

For example, the VAD may be a blood pump as published e.g. in U.S. Pat.No. 5,911,685, which is particularly arranged for a temporary placementor implantation into the left or right heart of a patient.

Preferably, the VAD is a low inertia device by comprising, but not beinglimited to, one or more of the following characteristics: (1) moving, inparticular rotating, parts, for example a rotor or impeller, of the VADmay comprise low masses by being made of a low weight material, such asplastic materials, synthetic materials or the like; (2) a driving means,such as an electric motor, may be arranged near, preferably very near,most preferably adjacent, to a part, for example a rotor or impeller,driven by the motor, and, if catheter-based, should preferably notinclude any rotational drive cable or drive wire, but electric wiring;(3) a coupling or connection, for example a shaft, of the motor with apart, for example a rotor or impeller, driven by the motor may be madeshort; (4) all moving parts, in particular rotating parts, of the VADmay have small diameters. Note that the foregoing list ofcharacteristics does not claim to be complete, i.e. the device maycomprise further or alternative characteristics that make the device alow inertia device.

DETAILED DESCRIPTION OF THE DRAWINGS

Hereinafter the invention will be explained by way of examples withreference to the accompanying drawings; in which

FIG. 1 shows one exemplary embodiment of a VAD placed through the aortaand extending through the aortic valve into the left ventricle of aheart, and a block diagram of an exemplary embodiment of the controldevice for the VAD;

FIG. 2 shows a side view of the exemplary VAD of FIG. 1 in more detail;

FIG. 3 shows a diagram with exemplary signal waveforms that represent,a) the aortic pressure (AoP(t)), b) the left ventricular pressure(LVP(t)), c) an ECG (ECG(t)), and d) a speed command signal trajectory(n_(VAD) ^(set)(t)), and with e) a corresponding sequence of triggersignals (σ(0), for illustrating the principle of pulsatile speed controlto restore and/or maintain blood pulsatility by means of the VAD ofFIGS. 1 and 2 under control of the control device of FIG. 1;

FIG. 4 shows an electrical equivalent circuit of an electrical modelapproximating the so-called Windkessel effect in the aorta;

FIG. 5 shows the results of five different simulation scenarios withrespect to the blood flow of the heart Q_(heart)(t) and blood flow ofthe pump Q_(pump)(t) (upper plots) and aortic pressure AoP(t) (lowerplots).

DETAILED DESCRIPTION

FIG. 1 shows a catheter-based rotational blood pump (in the followingcalled “blood pump”) on the left hand side, which is described herein asone exemplary embodiment of a VAD. This exemplary blood pump is shown inmore detail in FIG. 2.

As noted above, one important physical prerequisite which was found bythe inventors to be fulfilled by the VAD to be used for the applicationsproposed herein is the absence of any relevant inertia. The rotary bloodpumps such as a blood pump of the catheter-based pump type shown in FIG.2 do not have any relevant inertia which would hinder the implementationof the proposed speed control scenarios with within-a-beat speedmodulation.

The blood pump is based on a catheter 10 (catheter-based blood pump), bymeans of which the blood pump is temporarily introduced through theaorta 12 and the aortic valve 15 into the left ventricle 16 of a heart.As shown in more detail in FIG. 2, the blood pump comprises in additionto the catheter 10 a rotary pumping device 50 fastened to the end of acatheter tube 20. The rotary pumping device 50 comprises a motor section51 and a pump section 52 located at an axial distance therefrom. A flowcannula 53 is connected to the pump section 52 at its one end, extendsfrom the pump section 52 and has an inflow cage 54 located at its otherend. The inflow cage 54 has attached thereto a soft and flexible tip 55.The pump section 52 comprises a pump housing with outlet openings 56.Further, the pumping device 50 comprises a drive shaft 57 protrudingfrom the motor section 51 into the pump housing of the pump section 52.The drive shaft 57 drives an impeller 58 as a thrust element by means ofwhich, during operation of the blood pump, blood can be sucked throughthe inflow cage 54 and discharged through the outlet openings 56.

The pumping device 50 can also pump in the reverse direction whenadapted accordingly, e.g. as required when the blood pump is placed inthe right heart. In this regard and for the sake of completeness, FIG. 1shows the rotary blood pump as one particular example of a VAD locatedin and for assistance of the left heart. For assistance of the rightheart, the rotary blood pump of the present example may be temporarilyintroduced into the right heart from the vena cava and located in theright heart so that blood can be ejected into the pulmonary artery. Inthis configuration, the blood pump may be configured for sucking inblood from the vena cava or from the right ventricle and for ejectingthe blood into the pulmonary artery. That is to say, the principles andfunctionalities described by the one particular embodiment may betransferred correspondingly for right-sided heart assistance. Thus, nodetailed description is required.

In FIGS. 1 and 2, three lines, two signal lines 28A and 28B and apower-supply line 29 for suppling an electrical current to the motorsection 51, pass through the catheter tube 20 of the catheter 10 to thepumping device 50. The two signal lines 28A, 28B and the power-supplyline 29 are attached at their proximal end to a control device 100. Itgoes without saying that there may be additional lines for furtherfunctions; for example, a line for a purge fluid (not shown) may passthrough the catheter tube 20 of the catheter 10 to the pumping device 50as well. Additional lines may be added based on different sensingtechnologies.

As shown in FIG. 2, the signal lines 28A, 28B are parts of bloodpressure sensors with corresponding sensor heads 30 and 60,respectively, which are located externally on the housing of the pumpsection 52. The sensor head 60 of the first pressure sensor isassociated with signal line 28B. The signal line 28A is associated withand connected to the sensor head 30 of the second blood pressure sensor.The blood pressure sensors may, for example, be optical pressure sensorsfunctioning according to the Fabry-Perot principle as described in U.S.Pat. No. 5,911,685 A, in which case the two signal lines 28A, 28B areoptical fibers. However, other pressure sensors may be used instead.Basically, signals of the pressure sensors, which carry the respectiveinformation on the pressure at the location of the sensor and which maybe of any suitable physical origin, e.g. of optical, hydraulic orelectrical, etc., origin, are transmitted via the respective signallines 28A, 28B to corresponding inputs of a data processing unit 110 ofthe control device 100. In the example shown in FIG. 1, the pressuresensors are arranged so that the aortic pressure AoP(t) is measured bysensor head 60 and the left ventricular pressure LVP(t) is measured bysensor head 30.

The data processing unit 110 is configured for acquisition of allexternal and internal signals, for actual signal processing, whichincludes for example calculation of a difference between two pressuresignals as a basis for estimating pump flow, for signal analysis todetect characteristic events during the cardiac cycle based on theacquired and calculated signals, and for generating a sequence oftrigger signals σ(t) by means of a trigger signal generator, fortriggering a speed command signal generator 120 (see details below).

The data processing unit 110 is connected via corresponding signal linesto additional measurement devices 300, such as a patient monitoring unit310 and an electrocardiograph 320; these devices are just two examples,i.e. other measuring devices may provide useful signals and therefore beused as well. The electrocardiograph 320 provides an ECG signal ECG(t)to the data processing unit 110.

The control device 100 further comprises a user interface 200 comprisinga display 210 and a communication interface 220. On the display 210,setting parameters, monitored parameters, such as measured pressuresignals, and other information is displayed. Further, by means of thecommunication interface 220, the user of the control device 100 cancommunicate with the control device 100, e.g. to change settings of thewhole system.

The data processing unit 110 is particularly configured to derive orpredict the time of occurrence of one or more predefined characteristicevents during the cardiac cycle of the assisted heart by means ofreal-time analysis of current signal values which are used forgeneration of a sequence of trigger signals σ(t) by means of a triggersignal generator. The resulting sequence of trigger signals σ(t) isforwarded to the speed command signal generator 120 to trigger speedcommand signal changes.

Further, the data processing unit 110 is configured to analyze previousvalues of these speed command signals n_(VAD) ^(set)(t), as well. Thatis, the data processing unit 110 is also configured to predict the timeof occurrence of the at least one predefined characteristic event in theupcoming cardiac cycle based on the stored information about thecharacteristic events occurring during the current and/or previouscardiac cycles.

One particular characteristic event of the cardiac cycle may be thebeginning of contraction of the heart at the beginning of the systolicphase. The detected occurrence or the predicted occurrence of suchcharacteristic event is used as an event for synchronizing the pulse ofthe speed command signal n_(VAD) ^(set)(t) as proposed herein with thecardiac cycle.

The speed command signal generator 120 is configured to generate andadjust the speed command signal n_(VAD) ^(set)(t) of the pumping device50 and to provide it to a speed control unit 130 either in a feedforwardsetup as an event-based command signal generator (first setup) or in anouter feedback closed-loop setup for pressure control (second setup).

In the first setup, the speed command signal generator 120 is triggeredby at least one sequence of trigger signals σ(t) which is provided bythe data processing unit 110. In the second setup, the speed commandsignal n_(VAD) ^(set)(t) is provided by a pressure control algorithm (asthe command signal generator 120) which operates in an outer feedbackloop and is fed with external and internal signals by the dataprocessing unit 110, and triggered by at least one sequence of triggersignals σ(t) provided by the data processing unit 110 to achieve thedesired minimum pulsatility ΔAoP(h).

Accordingly, the speed control unit 130 controls the speed n_(VAD)(t) ofthe VAD, in accordance with the speed command signal n_(VAD) ^(set)(t),by supplying a motor current I_(VAD)(t) to the motor section 51 of thepumping device 50 via the power-supply line 29 that leads through thecatheter tube 20. The current level of the supplied motor currentI_(VAD)(t) corresponds to the electrical current currently required bythe pumping device 50 to establish the target speed level as defined bythe speed command signal n_(VAD) ^(set)(t). Via the power-supply line29, the pump also communicates with the control unit 100.

A measuring signal such as the supplied motor current I_(VAD)(t) whichis used as a representative signal of an internal signal of the controldevice 100 is provided to the data processing unit 110 for furtherprocessing.

According to the first aspect of the present invention, the controldevice 100 is configured for altering the speed of the blood pump ofFIGS. 1 and 2 as an exemplary embodiment of a VAD for heart assistance.

The control device 100 is particularly configured to alter the speed ofthe blood pump 50 within a cardiac cycle of the assisted heart,resulting in a change of the blood flow through the pump, the speedalteration of which is synchronized with the heartbeat by means of atleast one event per cardiac cycle which is related to a predeterminedevent in the cardiac cycle. That is to say, the speed command signalgenerator 120 may be triggered by at least one sequence of triggersignals σ(t) provided by the trigger signal generator of the dataprocessing unit 110 which obtains information on at least one particularevent in the cardiac cycle the occurrence of which is detected, thecorresponding signal information being used to set the sequence oftrigger signals σ(t).

But it should be noted that the trigger signal generator which providesthe sequence of trigger signals σ(t) may rely on more than one event inthe cardiac cycle to be detected during each cardiac cycle and to beanalyzed to derive a corresponding sequence of trigger signals σ(t) foradjusting the command signal n_(VAD) ^(set)(t) and, thus, for alteringthe speed n_(VAD)(t) of the blood pump 50.

As discussed above, the blood pump comprises the rotary pumping device50, with the (rotational) speed n_(VAD)(t) of the impeller beingcontrolled by speed control unit 130. The speed command signal n_(VAD)^(set)(t) of the blood pump is adjusted by the command signal generator120.

According to a first embodiment of the proposed change of blood flowproduced by the blood pump, the control device 100, in particular thespeed command signal generator 120, is configured to adjust the speedcommand signal n_(VAD) ^(set)(t) of the rotary pumping device 50 so thatthe resulting speed n_(VAD)(t) of the VAD is altered to generate aVAD-induced blood flow Q_(VAD)(t), which induces a pressure pulse withineach cardiac cycle.

For a better understanding, an example of the potential effect of thespeed alteration is illustrated in FIG. 3. FIG. 3 shows a diagram withexemplary waveforms.

The waveforms in FIG. 3a ) represent the aortic pressure signaldistinguishing between physiological (non-assisted) aortic pressureAoP(t) (dashed line) and desired (assisted) aortic pressure

(t) (solid line).

The waveform in FIG. 3b ) represents the signal for the left ventricularpressure LVP(t) with examples for characteristic pressure values and/orevents in the cardiac cycle which may be used for generating or derivinga sequence of trigger signals σ(t).

The waveform in FIG. 3c ) represents an ECG signal.

The diagram of FIG. 3 illustrates by way of one example the principle ofa pulsatile blood pressure restoration and maintenance using the bloodpump of FIGS. 1 and 2 under control of the control device 100 in FIG. 1.

To this end, FIG. 3d ) shows one particular example of a speed commandsignal n_(VAD) ^(set)(t).

In FIG. 3e ), a corresponding sequence of trigger signals σ(t) isillustrated.

The speed command signal n_(VAD) ^(set)(t) is used for the pump speedalteration which corresponds to the signal output of the speed commandsignal generator 120, and which is forwarded to the speed control unit130. The sequence of trigger signals σ(t) is the basis for theevent-based speed command signal generation or the event-basedclosed-loop pressure control resulting in an altered speed commandsignal n_(VAD) ^(set)(t), the alteration of which is synchronized withthe heartbeat.

The command signal n_(VAD) ^(set)(t) represents a speed increase from abasic speed level

n _(VAD) ^(set)(t)=n _(VAD) ^(set,basic)(j)

to an increased speed level

n _(VAD) ^(set)(t)=n _(VAD) ^(set,basic)(j)+Δn _(VAD) ^(set)(j)

at the beginning of a speed pulse, wherein Δn_(VAD) ^(set)(j) representsthe speed difference during the speed pulse.

In FIG. 3, the beginning of the speed pulse is synchronized with the endof diastole. Further, the speed decrease from the increased speed level

n _(VAD) ^(set)(t)=n _(VAD) ^(set,basic)(j)+Δn _(VAD) ^(set)(j)

back to the basic speed level

n _(VAD) ^(set)(t)=n _(VAD) ^(set,basic)(j)

at the end of the speed pulse is also shown.

In FIG. 3, the end of the speed pulse is synchronized with the end ofsystole. These speed alterations each represent possible implementationsof speed alteration for achieving the desired minimum pulsatility asdiscussed in the general section herein.

The speed decrease is triggered so that a the pulse of the speed commandsignal n_(VAD) ^(set)(t) after a heart rate dependent pulse durationτ^(assist)(h), i.e. the pulse duration is adapted to the heart rateHR(h). That is to say, the command signal generator 120 is configured togenerate a speed pulse with a heart rate dependent pulse duration.

Alternatively, the speed decrease can be triggered so that apredetermined pulse duration τ^(pulse)(j) is achieved. To this end, thecommand signal generator 120 can be configured to generate a speed pulsewith a predetermined pulse duration τ^(pulse)(j).

In the shown example (FIG. 3d ), the speed increases by the speeddifference Δn_(VAD) ^(set)(j) at the beginning of the speed pulse endshere e.g. at time point t^(LVP) _(j,ED), and the speed decrease at theend of the speed pulse ends here e.g. at time point t^(AoP) _(j,ED).

Preferably, in operation, the speed command signal generator 120 isconfigured to control pulsatility ΔAoP(h) by adjusting the speeddifference Δn_(VAD) ^(set)(h) accordingly. As discussed above, a desiredminimum pulsatility in the range of Δ

(h)=[15 . . . 30] mmHg is considered as sufficient so that a deficiencyin the vWF may not occur and/or microvascular perfusion may be improved.

Further, as discussed above, the data processing unit 110 is configuredto measure and/or calculate the current mean arterial blood pressure perheartbeat AoP(h) and to supply the current value to the speed commandsignal generator 120. To this end, the speed command signal generator120 is further configured to adjust the speed command signal n_(VAD)^(set)(t) to preferably avoid a drop of the arterial blood pressurebelow a predetermined threshold value AoP(h)≥AoP _(thr)(h).

As discussed in the general section, restoration and/or maintenance of asufficient minimum blood pressure pulsatility can be achieved byaltering the speed of the rotary pumping device 50 so that theVAD-induced blood flow Q_(VAD)(t) is reduced substantially duringdiastole of the cardiac cycle and/or is increased substantially duringsystole of the cardiac cycle. Thus, in particular embodiments, the speedcommand signal generator 120 is configured to adjust the speed commandsignal n_(VAD) ^(set)(t) so that in the diastolic phase of the cardiaccycle of the assisted heart the blood volume ejected to the aorta (orpulmonary artery) is low such that a predetermined volume remains in theleft (right) ventricle and the rotary pumping device 50, together withthe left (right) ventricle, co-ejects appropriate blood volumes duringsystole. In other words, the diastolic speed reduction also allows theheart to fill adequately, so that a systolic co-ejection of blood fromthe rotary pumping device 50 and the native heart is possible. In thisregard, the inventors have found that the pump and the native heartshould induce a total peak flow during systole of

Q _(total|max)(h)=Q _(heart|max)(h)+Q _(pump|max)(h)>6 L/min . . . 10L/min,

resulting in total ejected volumes of

EV(h)=EV_(heart)(h)+EV_(pump)(h)=40 . . . 70 ml,

so that the desired minimum pulsatility Δ

(h)≥15 . . . 30 mmHg can be achieved. Nevertheless, the targeted desiredminimum pulsatility Δ

(h) will not be a fixed value, but may vary based on the recruitment ofvWF. Moreover, if the native pulsatility of a weakened heart is alreadyhigher than the desired minimum pulsatility, then the pulsatility willof course not necessarily be reduced.

The inventors have validated the values stated for peak flows perheartbeat of the pump Q_(pump|max)(h) and the heart Q_(heart|max)(h) andthe corresponding total ejection volumes per heartbeat of the pumpEV_(pump)(h) and the heart EV_(heart)(h) by means of a mathematicalmodel of an electrical equivalent circuit. The model used is illustratedin FIG. 4.

FIG. 4 shows the circuit of the electrical model approximating thedynamics of the so-called Windkessel effect in the aorta when blood isejected by the heart. The electrical model consists of a resistor(R₁=0.05 Ohm) representing the resistance of the aortic valve in serieswith a series connection of another resistor (R₂=1.32 Ohm) representingthe resistance of the peripheral system of the arteries, and a capacitor(C₂=1.7 F) representing the arterial compliance. Further, in the model,the (residual) cardiac output Q_(heart)(h) and the blood flow of thepump Q_(pump)(h) are assumed as current sources. Representing a rotatoryblood pump, a standard pump Impella® 5.0 was used; for more details,reference is made to Catanho et al., “Model of Aortic Blood Flow Usingthe Windkessel Effect”, Beng 221, Mathematical Methods inBioengineering, Report, 2012.

FIG. 5 represents the results of five different simulation scenarios.The table below shows the results of the five different simulationscenarios with additional information on total blood flow for aheartbeat j (Q_(total)(j)) and corresponding pulsatility (ΔAoP(j)).

In FIG. 5, from the left to the right, the considered scenarios {circlearound (1)} to {circle around (2)} were the following:

Scenario {circle around (1)}—“healthy heart”: A native heart function isassumed, resulting in peak flows of the heart Q_(heart|max)(j)=15 L/minand a pulsatility of ΔAoP(j)=40 mmHg (120/80 mmHg) with a common meanaortic blood pressure AoP(j)=105.4 mmHg.

Scenario {circle around (2)}—“weakened heart, no assistance”: The heartfunction is reduced to a third of the native function, resulting in apeak flow of the heart Q_(heart|max)(j)=5.4 L/min and a very lowpulsatility of ΔAoP(j)=14.5 mmHg (42/28 mmHg) with an unphysiologicallylow mean aortic blood pressure of AoP(j)=36.8 mmHg while no pump isimplanted.

Scenario {circle around (3)}—“full unloading (P4)”: The weakened heartis assisted by a pump at speed level P4 with the aim of generatingmaximum flow, resulting in a total peak flow ofQ_(total|max)(j)=Q_(heart|max)(j)+Q_(pump|max)(j)=8.5 L/min and amoderate pulsatility of ΔAoP(j)=17.2 mmHg (96/79 mmHg) with aphysiologically mean aortic blood pressure of AoP(j)=89.8 mmHg.

Scenario {circle around (4)}—“low pulsatility (P4/P2)”: The weakenedheart is assisted by a pump, the speed of which is altered with thespeed of scenario {circle around (3)} (P4) at systole and low speed (P2)at diastole, resulting in a total peak flow ofQ_(total|max)(j)=Q_(heart|max)(j)+Q_(pump|max)(j)=8.5 L/min and a highermoderate pulsatility of ΔAoP(j)=20.4 mmHg (78/58 mmHg) compared toscenario {circle around (3)} at a lower mean aortic pressure ofAoP(j)=70.6 mmHg.

Scenario {circle around (5)}—“high pulsatility (P9/P2)”: The weakenedheart is assisted by a pump, the speed of which is altered with thehighest possible speed (P9) at systole and low speed (P2) at diastole,resulting in a high total peak flow ofQ_(total|max)(j)=Q_(heart|max)(j)+Q_(pump|max)(j)=10.3 L/min and thehighest possible pulsatility of ΔAoP(j)=27.4 mmHg (95/69 mmHg) at amoderate mean aortic pressure of AoP(j)=85.2 mmHg.

It should be noted that in Scenario {circle around (3)}-{circle around(5)} it is assumed that the heart ejects the same amount during systoledespite varying degrees of diastolic unloading by the pump.

Values for heartbeat j Q_(heart)|_(max) Q_(pump)|_(max) Q_(total)EV_(heart) EV_(pump) ΔAoP AoP Scenario [L/min] [L/min] [L/min] [ml] [ml][mmHg] [mmHg] {circle around (1)} “healthy heart” 15.0 0.0 4.34 72.3 0.040.0 105.4 {circle around (2)} “weakened 5.4 0.0 1.51 25.2 0.0 13.5 36.8heart, no assistance” {circle around (3)} “full unloading 5.4 3.1 3.8125.2 38.2 17.2 89.8 (P4)” {circle around (4)} “low pulsatility 5.4 3.12.94 25.2 23.8 20.4 70.6 (P4/P2)” {circle around (5)} “high pulsatility5.4 4.9 3.54 25.2 33.8 27.4 85.2 (P9/P2)”

In summary, the simulation results underline the fact that the speedalteration can either focus on increased pulsatility while acceptingreduced mean aortic pressure or focus on increased mean aortic pressurewhile accepting reduced pulsatility. Physical and physiologicalconstraints were taken into consideration here, such as very low inertiaand hemolysis.

In particular, the data processing unit 110 is configured to trigger thespeed command signal generator 120 so that the pulse of the speedcommand signal n_(VAD) ^(set)(t) begins and/or ends at the detected orpredicted time of occurrence of at least one predetermined event in thecardiac cycle. The at least one sequence of trigger signals σ(t) whichis generated by the trigger signal generator of the data processing unit110 is provided to the speed command signal generator 120.

In a preferred embodiment and as illustrated in FIG. 3, the speedcommand signal generator 120 is configured to initialize the increase ofthe speed command signal n_(VAD) ^(set)(t) a predetermined time intervalτ^(incr)(h) before a characteristic event of the cardiac cycle occurs,which is used as a basis for generating the sequence of trigger signalsσ(t). This sequence of trigger signals σ(t) can be used to change thepump speed in a moderate manner to avoid suction, blood damage, etc., orto allow the pump speed increase in a timely manner to address the phaseshift between a change in speed and the resulting change in pressure(compliance of vasculature and inertia of blood) for the systolicco-ejection.

In the example illustrated in FIG. 3, the starting time of contractionof the left ventricle is used as the characteristic time taken intoaccount for the sequence of trigger signals σ(t) generated by thetrigger signal generator. The contraction of the left ventricle startsimmediately after the R-wave occurs in the corresponding ECG signal.Thus, the speed command signal generator 120 may be configured to derivea sequence of trigger signals σ(t) based on the ECG signal, which isprovided to the data processing unit 110. The data processing unit 110may be configured to receive the ECG signal from an (external) ECGdevice 320 and to generate the sequence of trigger signals σ(t) by meansof the trigger signal generator.

As mentioned above, another measuring signal may be used by the dataprocessing unit 110 for generating the sequence of trigger signals σ(t),showing e.g. the beginning of left atrial contraction which can be usedas an event, the time of occurrence of which precedes the beginning ofthe systolic ejection phase. For example, in FIG. 3b ) somecharacteristic values and times are marked as examples on the signal forthe left ventricular pressure LVP(t), namely the minimum valueLVP_(min)(j), the maximum value LVP_(min)(j), its maximum change overtime dLVP(j)/dt|_(max), and its minimum change over timedLVP(j))/dt|_(min).

To sum up, the speed command signal generator 120 synchronizes theadjustment of the speed command signal n_(VAD) ^(set)(t) with thecardiac cycle by means of at least one sequence of trigger signals σ(t)which is provided by the data processing unit 110 such that the speedpulse is initialized before the beginning of ventricular contractionand/or the occurrence of the R-wave in the ECG signal.

The predetermined time interval τ^(incr)(h) for initializing theincrease of the speed command signal n_(VAD) ^(set)(t) may be set, forexample, to about τ^(incr)(h)=150 ms, preferably τ^(incr)(h)=100 ms,most preferably τ^(incr)(h)≤100 ms before the associated characteristicevent in the cardiac cycle. The inventors have further found that it canbe ensured by the predetermined time interval τ^(incr)(h) that the bloodflow is not accelerated too fast, which is assumed to reduce thelikelihood of blood damage and/or of undesired hemodynamic effects.Thus, the speed command signal generator 120 is configured to adjust thespeed command signal n_(VAD) ^(set)(t) such that the speed n_(VAD)(t) ofthe VAD is altered smoothly.

As one particular example, FIG. 3d ) shows a speed command signaln_(VAD) ^(set)(t) with a ramp for increasing or decreasing the speedn_(VAD)(t) of the VAD linearly, but other forms may be possible as well,such as an exponential speed increase or decrease.

Finally, the speed command signal generator 120 is configured to adjustthe speed n_(VAD)(t) of the VAD back to the initial speed level n_(VAD)^(set,basic)(t) to end a current speed pulse after the predeterminedpulse duration τ^(pulse)(h).

Alternatively or additionally, the speed command signal generator 120 isconfigured to adjust the speed command signal n_(VAD) ^(set)(t) foraltering the speed n_(VAD)(t) of the VAD to end a current speed pulsewhen a predetermined characteristic event of the cardiac cycle occurs.

In a preferred embodiment, the predetermined event is the beginning ofrelaxation of the assisted heart and/or the closing of the aortic valve.Here, the predetermined time interval τ^(red)(h) for initializing thereduction of the speed command signal n_(VAD) ^(set)(t) before, duringor after a predetermined characteristic event in the cardiac cycle mayalso be taken into account. Preferably, the trigger for terminating thespeed pulse is part of the sequence of trigger signals σ(t) and isprovided by the data processing unit 110 a time interval τ^(red)(h)before ventricular relaxation begins. Preferably, this trigger signal isbased on a prediction of the beginning of ventricular relaxationdetected during previous cardiac cycles.

For example, the closing of the aortic valve can be determined when theleft ventricular pressure LVP(t) drops below the aortic pressure AoP(t)or, correspondingly, when the pressure difference between the inlet 54and the outlet 56 of the flow cannula 53 becomes lower than zero.

The data processing unit 110 is further configured to derive thesequence of trigger signals σ(t) from at least one signal that comprisesinformation relating to the closing of the aortic valve of the assistedheart as a characteristic event in the cardiac cycle.

For example, useful signals may be a measuring signal representing aleft ventricular pressure LVP(t) of the assisted heart and/or the aorticpressure AoP(t) adjacent to the assisted heart. If the blood pump isconfigured for assistance of and placement into the right side of theheart, the signal may be a measuring signal representing a bloodpressure in the vena cava CVP(t) adjacent to the assisted heart and/orright ventricular pressure RVP(t) and/or a blood pressure in thepulmonary artery PAP(t) adjacent to the assisted heart.

The data processing unit 110 is configured to derive a sequence oftrigger signals σ(t) from a required motor current I_(VAD)(t) that isprovided by the speed control unit 130 to the rotary pumping device 50.As discussed elsewhere herein, the required motor current I_(VAD)(t)reflects the energy required by the rotary pumping device 50 to followthe set speed value. Thus, the command signal generator 120 may betriggered by a corresponding sequence of trigger signals σ(t) providedby the data processing unit 110.

Preferably, the data processing unit 110 is configured to receive, storeand analyze at least one measuring signal containing characteristicinformation of the circulatory system and of the cardiac cycle in orderto predict at least one event per heartbeat based on analysis results ofprevious cardiac cycles. Most preferably, the data processing unit 110is configured to analyze at least two measuring signals to filter theimpact of the pump-induced pressure changes so that characteristicevents in the cardiac cycle may be reliably detected.

1. A control device for controlling rotational speed (n_(VAD)(t)) of anon-pulsatile ventricular assist device (VAD) by an event-basedwithin-a-beat control strategy, wherein the control device is configuredto: alter the rotational speed (n_(VAD)(t)) of the VAD within a cardiaccycle of an assisted heart; and synchronize the alteration of therotational speed (n_(VAD)(t)) with a heartbeat by at least one sequenceof trigger signals (σ(t)) that is related to at least one predeterminedcharacteristic event in the cardiac cycle.
 2. The control device ofclaim 1, wherein the control device is configured to alter therotational speed (n_(VAD)(t)) of the VAD for a predetermined pulseduration (τ^(pulse)(h)) or a heart rate dependent pulse duration(τ^(assist)(h)) to generate a predetermined desired minimum pulsatility(Δ

(h)) in an artery of interest within the cardiac cycle, and tosynchronize at least one of a beginning and an end of the rotationalspeed alteration by the at least one sequence of trigger signals (σ(t)).3. The control device of claim 2, wherein the control device isconfigured to generate a speed command signal (n_(VAD) ^(set)(t)) forthe alteration of the rotational speed (n_(VAD)(t)) of the VAD so thatthe predetermined desired minimum pulsatility (Δ

(h)) is achieved either in a first setup by an open-loop control,wherein the speed command signal (n_(VAD) ^(set)(t)) is alternatedbetween predefined rotational speed levels using a command signalgenerator or in a second setup by a closed-loop pressure control in afeedback system, wherein the speed command signal (n_(VAD) ^(set)(t)) isautomatically set for each heartbeat (h).
 4. The control device of claim3, wherein the control device is configured to adjust the speed commandsignal (n_(VAD) ^(set)(t)) to achieve the predetermined desired minimumpulsatility (Δ

(h)) in the second setup.
 5. The control device of claim 2, wherein thecontrol device is configured to alter the rotational speed (n_(VAD)(t))of the VAD to generate the predetermined desired minimum pulsatility (Δ

(h)) only in y out of x consecutive cardiac cycles of the assistedheart, wherein x is an integer greater than 2 and y is an integer withy≤x.
 6. The control device of claim 5, wherein the control device isconfigured to set the rotational speed (n_(VAD)(t)) of the VAD during atleast y of the other x minus y consecutive cardiac cycles of theassisted heart, so that a mean arterial blood pressure per heartbeat(AoP(h)) remains above a predetermined threshold value (AoP _(thr)(h)).7. The control device of claim 2, wherein the control device is furtherconfigured to adjust a speed command signal (n_(VAD) ^(set)(t)) so thata mean arterial blood pressure per heartbeat (AoP(h)) remains above apredetermined threshold value (AoP _(thr)(h)).
 8. The control device ofclaim 2, wherein the control device is configured to initialize anadjustment of a speed command signal (n_(VAD) ^(set)(t)) a predeterminedfirst time interval (τ^(incr)(h)) before the at least one predeterminedcharacteristic event occurs.
 9. The control device of claim 8, whereinthe control device is configured to end the adjustment of the speedcommand signal (n_(VAD) ^(set)(t)) in accordance with at least one of:after the predetermined pulse duration (Σ^(pulse)(h))), after the heartrate dependent pulse duration (τ^(assist)(h)), with an occurrence of oneof the at least one predetermined characteristic event in the cardiaccycle, and a predetermined second time interval (τ^(red)(h)) before orwhen the at least one predetermined event in the cardiac cycle occurs.10. The control device of claim 1, wherein the control device isconfigured to derive one of the at least one sequence of trigger signals(σ(t)) from an electrical current which is supplied to an actuator ofthe VAD.
 11. The control device of claim 10, wherein the control deviceis configured to distinguish changes in the electrical current due tothe alteration of the rotational speed (n_(VAD)(t)) of the VAD fromchanges in the electrical current caused by the assisted heart passingthrough the cardiac cycle.
 12. The control device of claim 1, whereinthe control device is configured to derive the at least one sequence oftrigger signals (σ(t)) from at least one signal being a processedmeasuring signal, with the processed measuring signal representing atleast one of the following physical quantities: a blood pressuredifference between an outlet of the VAD for blood ejection and an inletof the VAD for sucking blood in, a blood pressure in a ventricle of theassisted heart, a blood pressure in the aorta adjacent to the assistedheart, a blood pressure in the vena cava adjacent to the assisted heart,and a blood pressure in the pulmonary artery adjacent to the assistedheart.
 13. The control device of claim 1, wherein the control device isconfigured to: determine from at least one processed measuring signalcharacteristic information about the circulatory system within a cardiaccycle; and determine the at least one predetermined characteristic eventfor an upcoming cardiac cycle based on characteristic informationdetermined during previous cardiac cycles.
 14. The control device ofclaim 13, wherein the control device is configured to determine from atleast two processed measuring signals an impact of the alteration of therotational speed (n_(VAD)(t)) of the VAD when deriving or predicting theat least one predetermined characteristic event.
 15. The control deviceof claim 1, wherein the control device is configured to control therotational speed (n_(VAD)(t)) of the VAD so that in a diastolic phase ofthe cardiac cycle of the assisted heart an amount of blood ejected intothe aorta or into the pulmonary artery is such that a blood volumeremains in the corresponding ventricle and co-ejection of the VAD andthe ventricle during systole results in a predetermined minimum totalpeak blood flow (Q_(total|max)(h)).
 16. The control device of claim 1,wherein the control device is configured to do at least one of: increasethe rotational speed (n_(VAD)(t)) of the VAD during systole of theassisted heart or to reduce the rotational speed (n_(VAD)(t)) of the VAD(50) during diastole of the heart.
 17. The control device of claim 1,wherein the control device is configured to alter the rotational speedof the VAD only when an average VAD-induced blood flow can be set abovea currently required minimum blood flow demand of the assisted heart.18. A VAD for assistance of a heart, the VAD comprising a control devicefor controlling the rotational speed (nVAD(t)) of the VAD, by means ofan event-based within-a-beat control strategy, wherein the controldevice is configured to: alter the rotational speed (n_(VAD)(t)) of theVAD within the cardiac cycle of the assisted heart; and synchronize thealteration of the rotational speed (n_(VAD)(t)) with the heartbeat by atleast one sequence of trigger signals (σ(t)) that is related to at leastone predetermined characteristic event in the cardiac cycle.
 19. The VADof claim 18, wherein the VAD is a low inertia device by comprising oneor more of the following characteristics: moving parts of the VADcomprise low masses by being made of a low weight material; a drivingmeans is arranged near to a part driven by the motor; a coupling orconnection of the motor with a part driven by the motor is short; allmoving parts of the VAD have small diameters.
 20. The VAD of claim 18,wherein the VAD is a non-pulsatile rotational blood pump.
 21. The VAD ofclaim 18, wherein the VAD is catheter-based.
 22. The VAD of claim 21,wherein the driving means have no rotational drive cable or drive wire.23. The VAD of claim 19, wherein the driving means are an electricrotor.
 24. The VAD of claim 19, wherein the moving parts are rotating.25. The VAD of claim 19, wherein the moving parts are a rotor orimpeller.
 26. The VAD of claim 19, wherein the low weight material isplastic.
 27. The VAD of claim 19, wherein the driving means are arrangedvery near to the part.
 28. The VAD of claim 19, wherein the drivingmeans are arranged adjacent to the part.
 29. The VAD of claim 19,wherein the part is a rotor or impeller.
 30. The VAD of claim 19,wherein the coupling or connection is a shaft.
 31. The control device ofclaim 8, wherein the one characteristic event is at least one of: abeginning of ventricular contraction and an occurrence of the R-wave (R)in an electrocardiogram, ECG, signal led from the patient with theassisted heart.
 32. The control device of claim 9, wherein preferablythe at least one predetermined characteristic event in the cardiac cycleis at least one of the beginning of ventricular relaxation of theassisted heart and the closing of the aortic valve.
 33. The controldevice of claim 15, wherein the predetermined minimum total peak bloodflow is at least 6 L/min.
 34. The control device of claim 15, whereinthe predetermined minimum total peak blood flow is at least 8 L/min. 35.The control device of claim 16, wherein the rotational speed isincreased or reduced with respect to a basic speed level (n_(VAD)^(set,basic)(t)) in each case.